Method of delivering the intestines of human beings from bariumsulphate after barium meal examination

ABSTRACT

Lactulose has been found to be effective to expell barium sulphate from the intestines after barium meal examination.

United States Patent [191 Prout [4 1 Jan. 14,1975

[75] Inventor: Brian John Prout, Truro, England [73] Assignee: U.S. Philips Corporation, New

York, NY.

[22] Filed: Nov. 15, 1973 [21] Appl. No.: 416,037

[52] US. Cl. 424/180 [51] Int. Cl A0ln 9/00 [58] Field of Search 424/l 80 Primary Examiner-Elbert L. Roberts Attorney, Agent, or Firm-Frank R. Trifari; Norman N. Spain [57] ABSTRACT Lactulose has been found to be effective to expell barium sulphate from the intestines after barium meal examination.

4 Claims, No Drawings METHOD OF DELIVERING THE INTESTINES OF HUMAN BEINGS FROM BARIUMSULPHATE AFTER BARIUM MEAL EXAMINATION The invention relates to a new and novel method of delivering the intestines of human beings from barium sulphate after barium meal examination.

It has been found that barium sulphate often remains in the intestines of patients after a barium meal examination. This especially readily occurs in elderly patients.

When the retention of barium is not early recognized serious symptones may develop, such as abdominal pains, depression, mental confusion, constipation, abdominal distension and cramping.

It appeared that common laxative agents such as Senokot containing the active constituents of cassia angustifolia,

Bisacodyl, containing 4,4-(2-pyridylmethylen)diphenol diacetate as active ingredient and enemas, are not effective.

It has now been found, that barium sulphate can quite surprisingly be expelled from the intestines by administering orally a small but effective dose of lactulose.

Generally a dose of 3.3 gram of lactulose once or twice a day suffices. These doses even appeared to be effective in the treatment of patients who had the barium meal several weeks before the installation of the lactulose treatment. This is the more remarkable as in the meantime the bariumsulphate is completely dehydrated and the colon has lost of its normal propulsive movements.

It is note worthy that also in cases wherein severe conditions including constipation could develop the said low doses, which are substantially lower than those generally required to provoke diarrhoea, were sufficient to provoke the excretion of chalky stools and to completely deliver the intestines from bariumsulphate.

In view of the serious symptomes that may develop on barium sulphate retention, it is however recommended to start the administration of lactulose immediately after the barium meal X-ray examination. Alternatively lactulose may already be given together with or even just before the barium meal.

The duration of the treatment may vary from 1 to several weeks in the case some time lapsed between the barium meal examination and the curative treatment with lactulose. In the case the administration of lactulose is begun with at the time of the barium meal examination or shortly thereafter a treatment of l or 2 days to a week will suffice.

Lactulose may be administered in solid form either alone or in admixture with one or more carriers such as glucose, galactose or lactose. A very satisfactory method however is to administer the lactulose in the form of a syrup, for example one containing about 50% by weight of lactulose, about 5% by weight of lactose, about 8% by weight of galactose and the remainder water. This composition, which has a specific gravity of 1.33 (mg/ml), is called hereinafter Duphalac.

A dry composition may contain about 40% by weight of lactulose, about 4% by weight of lactose, about 6% by weight of galactose and the remainder dextrine maltose.

The lactulose may alternatively be worked into confectionery, candies, jelly drops, gum drops etc. each containing about 3 gram of lactulose. Colouring agents admitted for drugs, conserving agents such as sorbicacid and its salts, jellifying agents such as pcctine, thickening agents such as tragacanth gum, arabic gum and carboxymethylcellulose flavouring agents such as citric acid and tartaric acid may be employed.

The invention will now be described in greater detail with reference to the following case reports.

CASE 1 A 71-year-old woman was admitted as an emergency to the psychogeriatric assessment unit on Dec. 24, 1970 with a history of vague abdominal pains, depression, and mental confusion of recent onset. Her previous history indicated long-standing abdominal discomfort. In 1966 this had been investigated in the surgical department when barium meal had revealed no abnormality. Her abdominal symptoms had recurred intermittently, and in the autumn of 1970 further investigations had been carried out as a surgical outpatient, including on Nov. 25 a barium-meal examination which showed no abnormality.

On admission to the assessment unit she was noted to be depressed, disorientated, and intermittently confused. The colon was palpable and she was constipated.

Routine measures to clear the bowel were instituted. Senokot tablets (containing the active constituents of Cassia angustifolia) two daily proved unsuccessful, and Bisacodyl (4,4'-(Z-pyridylmethylene)diphenol diacetate) tablets two nightly together with repeated enemas also had no effect. These measures were continued for two weeks after admission, when physical examination showed a ballooned and empty rectum; the descending colon was no longer palpable but the ascending colon was palpable and thickened.

A barium-enema examination was requested but the preliminary plain x-ray picture of the abdomen on Jan. 7, 1971 showed a bowelfilled with what might be described as a barium cast and no further radiological examination was carried out at that time. After this examination 5 ml of Duphalac was administered orally twice daily. The patient was subsequently noted to excrete chalky stools, and a further x-ray film of the abdomen on Feb. 15 suggested some dilution of the colonic mass of barium. At that time she improved physically and was discharged home on 10 ml of Duphalac orally twice daily.

At follow-up on May 10 she had remained well, and a plain x-ray film of the abdomen showed that all residual barium had disappeared. Further review in Aug. indicated that her progress had been maintained, and subsequent investigation confirmed that there was no evidence of an organic obstruction in the gastrointestinal tract.

CASE 2 A -year-old widow was admitted to the general medical ward on Dec. 12, 1969 with an 8-week history of cramping lower abdominal pains, abdominal distension, and constipation. For about 6 months she had been experiencing intermittent upper abdominal discomfort, nausea, and slight looseness of the motions since the death of her husband. Her practitioner had arranged for a barium meal examination, which was carried out 6 weeks before her admission.

On examination the main physical findings were a distended abdomen with slightly increased bowel sounds and occasional visible peristalsis. Because of the possibility of an intestinal obstruction plain x-ray examination of the abdomen was carried out. This showed the large bowel filled with barium, but no fluid levels could be seen.

The patient was treated with soap enemas and Bisacodyl suppositories with no effect, and later oral Senokot was given in addition. This produced only a minimal effect and she was then treated with 5 ml of Duphalac orally twice daily. This induced the passage of chalky stools, and four weeks later the large bowel no longer contained barium on the plain x-ray film.

CASE 3 A 76-year-old man had recently been treated for a chest infection and had an episode of diarrhoea presumed to be due to tetracycline therapy. The diarrhoea had cleared. Barium meal examination showed a possible small gastric ulcer on the lesser curve. As he was reluctant to take any medication because of his previous experience with side effects he was advised to take regular and frequent meals with milk drinks between. The abdominal pain gradually worsened and he became increasingly constipated.

Five weeks after the barium-meal examination he was admitted to hospital. The only physical signs of note were an empty rectum, a firm enlarged prostate on rectal examination, and a tender palpable transverse and descending colon. A plain x-ray film of the abdomen showed the colon filled with barium.

Treatment with enemas was instituted but with no effect, and later Senokot and Bisacodyl suppositories were tried with only slight effect. The patient was then treated with 5 ml of Duphalac orally initially twice and then thrice daily. Loose chalky stools were then passed and 3 weeks later the bowel was seen to be clear of barium on the plain x-ray film.

CASE 4 A 70-year-old woman was admitted to hospital on Sept. 16, 1971 with a painful swollen left leg of 4 days duration. She was found to have mild maturity onset diabetes of one months duration. There was a history of anorexia and of weight loss of 19 kg in 3 months. She had been taking a small dose of prednisolone for 3 years because of exzema.

On examination she appeared a well-preserved, elderly woman. There were signs of a deep-vein thrombosis in the left leg but no appreciable abnormalities were found in the abdomen or other main systems. A midstream specimen of urine showed a coliform urinary infection.

She responded slowly to conservative measures. It was thought that an underlying neoplasm was possibly present, and a barium meal examination was carried out on Sept. 20. Apart from a calcified aorta no abnormality was noted. On Oct. 11 it was decided to carry out a barium-enema examination. The plain x-ray film showed that the colon was loaded with barium. She was then given Senokot and enemas in an attempt to empty the colon but this resulted in water diarrhoea. A repeat plain x-ray film on Oct. 14 showed the colon still filled with barium. She was treated with 5 ml of Duphalac orally twice daily after which she began to pass chalky stools, and on Oct. 21 the colon was seen to be clear of barium.

CASE 5 An 81-year-old woman was admitted to hospital for investigation of diarrhoea. she had been receiving ampicillin for 2 weeks because of a chest infection, and the diarrhoea, which started during therapy, had been persitent for 4 weeks. There had been no response to routine treatment of the diarrhoea, and as she was well preserved and had been previously fit she was referred to the gastroenterology department for further investigation.

A plain x-ray film of the abdomen and a barium enema examination showed nothing abnormal. A barium meal and follow through examination was carried out and was also clear, but after this the diarrhoea stopped for the first time for 7 weeks. An occasional formed motion was passed but lessned in frequency and amount until two weeks after the barium meal examination the patient was no longer able to open her bowels and complained of generalized abdominal discomfort. A plain x-ray film of the abdomen showed barium filling the entire large bowel.

There was no response to two enemas and treatment with Duphalac orally was instituted simultaneously in a dose of 10 ml twice daily. This cleared the bowel within l week. There was no recurrence of the original diarrhoea and no explanation was found for this sympton. It was presumed that pH changes induced by the barium and lactulose had further altered the bacterial flora of the gut which had initially been disturbed .by the antibiotic therapy. Subsequently she remained well.

What is claimed is:

l. A method of delivering the intestines of human beings from bariumsulphate after barium meal examination which method comprises administering to said human beings orally a daily effective dose of lactulose.

2. A method as claimed in claim 1 wherein lactulose is administered in a daily amount of 3.3 20 gram.

3. A method as claimed in claim 2 wherein lactulose is administered as a 50% by weight aqueous syrup.

4. A method as claimed in claim 1 wherein the administering of lactulose is begun with immediately after the barium meal examination.

UNITED STATES PATENT OFFICE CERTIFICATE OF CORRECTION Patent No. 3 50 70 Dated January 151975 Inventor(s) BRIAN JOHN PROUT It is certified that error appears in the above-identified patent and that said Letters Patent are hereby corrected as shown below:

Column 1, line 13, "symptones" should read symptoms.

line 18, after "gustifolia," insert as the same paragraph Bisacodyl, containing 4,4-(2-pyridylmethylen) diphenol diacetate as active ingredient and enemas, are not effective line 31, "bariumsulphate" should read barium sulphate line 32, cancel "of".

Column 2, line 2, "admitted" should read permitted Column 4, line 45, bariumsulphate" should read barium sulphate Signed and Scaled this twenty-second Day of July 1975 [SEAL] Arrest.-

RUTH C. MASON C. MARSHALL DANN Arresting Offiver Commissioner of Parents and Trademarks 

2. A method as claimed in claim 1 wherein lactulose is administered in a daily amount of 3.3 - 20 gram.
 3. A method as claimed in claim 2 wherein lactulose is administered as a 50% by weight aqueous syrup.
 4. A method as claimed in claim 1 wherein the administering of lactulose is begun with immediately after the barium meal examination. 